PMID- 19196673
OWN - NLM
STAT- MEDLINE
DCOM- 20090211
LR  - 20220410
IS  - 1533-4406 (Electronic)
IS  - 0028-4793 (Linking)
VI  - 360
IP  - 6
DP  - 2009 Feb 5
TI  - Chemotherapy, bevacizumab, and cetuximab in metastatic colorectal cancer.
PG  - 563-72
LID - 10.1056/NEJMoa0808268 [doi]
AB  - BACKGROUND: Fluoropyrimidine-based chemotherapy plus the anti-vascular 
      endothelial growth factor (VEGF) antibody bevacizumab is standard first-line 
      treatment for metastatic colorectal cancer. We studied the effect of adding the 
      anti-epidermal growth factor receptor (EGFR) antibody cetuximab to a combination 
      of capecitabine, oxaliplatin, and bevacizumab for metastatic colorectal cancer. 
      METHODS: We randomly assigned 755 patients with previously untreated metastatic 
      colorectal cancer to capecitabine, oxaliplatin, and bevacizumab (CB regimen, 378 
      patients) or the same regimen plus weekly cetuximab (CBC regimen, 377 patients). 
      The primary end point was progression-free survival. The mutation status of the 
      KRAS gene was evaluated as a predictor of outcome. RESULTS: The median 
      progression-free survival was 10.7 months in the CB group and 9.4 in the CBC 
      group (P=0.01). Quality-of-life scores were lower in the CBC group. The overall 
      survival and response rates did not differ significantly in the two groups. 
      Treated patients in the CBC group had more grade 3 or 4 adverse events, which 
      were attributed to cetuximab-related adverse cutaneous effects. Patients treated 
      with cetuximab who had tumors bearing a mutated KRAS gene had significantly 
      decreased progression-free survival as compared with cetuximab-treated patients 
      with wild-type-KRAS tumors or patients with mutated-KRAS tumors in the CB group. 
      CONCLUSIONS: The addition of cetuximab to capecitabine, oxaliplatin, and 
      bevacizumab resulted in significantly shorter progression-free survival and 
      inferior quality of life. Mutation status of the KRAS gene was a predictor of 
      outcome in the cetuximab group. (ClinicalTrials.gov number, NCT00208546.)
CI  - 2009 Massachusetts Medical Society
FAU - Tol, Jolien
AU  - Tol J
AD  - Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
FAU - Koopman, Miriam
AU  - Koopman M
FAU - Cats, Annemieke
AU  - Cats A
FAU - Rodenburg, Cees J
AU  - Rodenburg CJ
FAU - Creemers, Geert J M
AU  - Creemers GJ
FAU - Schrama, Jolanda G
AU  - Schrama JG
FAU - Erdkamp, Frans L G
AU  - Erdkamp FL
FAU - Vos, Allert H
AU  - Vos AH
FAU - van Groeningen, Cees J
AU  - van Groeningen CJ
FAU - Sinnige, Harm A M
AU  - Sinnige HA
FAU - Richel, Dirk J
AU  - Richel DJ
FAU - Voest, Emile E
AU  - Voest EE
FAU - Dijkstra, Jeroen R
AU  - Dijkstra JR
FAU - Vink-Borger, Marianne E
AU  - Vink-Borger ME
FAU - Antonini, Ninja F
AU  - Antonini NF
FAU - Mol, Linda
AU  - Mol L
FAU - van Krieken, Johan H J M
AU  - van Krieken JH
FAU - Dalesio, Otilia
AU  - Dalesio O
FAU - Punt, Cornelis J A
AU  - Punt CJ
LA  - eng
SI  - ClinicalTrials.gov/NCT00208546
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - N Engl J Med
JT  - The New England journal of medicine
JID - 0255562
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (KRAS protein, human)
RN  - 0 (Organoplatinum Compounds)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 04ZR38536J (Oxaliplatin)
RN  - 0W860991D6 (Deoxycytidine)
RN  - 2S9ZZM9Q9V (Bevacizumab)
RN  - 6804DJ8Z9U (Capecitabine)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras))
RN  - EC 3.6.5.2 (ras Proteins)
RN  - PQX0D8J21J (Cetuximab)
RN  - U3P01618RT (Fluorouracil)
SB  - IM
EIN - N Engl J Med. 2010 Dec 23;363(26):2573
CIN - N Engl J Med. 2009 Feb 5;360(6):623-5. PMID: 19196680
CIN - N Engl J Med. 2009 May 14;360(20):2134; author reply 2135-6. PMID: 19439750
CIN - N Engl J Med. 2009 May 14;360(20):2134-5; author reply 2135-6. PMID: 19445031
CIN - N Engl J Med. 2009 May 14;360(20):2135; author reply 2135-6. PMID: 19445032
CIN - N Engl J Med. 2009 May 14;360(20):2135; author reply 2135-6. PMID: 19445033
CIN - Immunotherapy. 2009 May;1(3):339-40. PMID: 20653090
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antibodies, Monoclonal/*administration & dosage/adverse effects
MH  - Antibodies, Monoclonal, Humanized
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use
MH  - Bevacizumab
MH  - Capecitabine
MH  - Cetuximab
MH  - Colorectal Neoplasms/*drug therapy/genetics/pathology
MH  - Deoxycytidine/administration & dosage/analogs & derivatives
MH  - Disease-Free Survival
MH  - ErbB Receptors/*antagonists & inhibitors/immunology/metabolism
MH  - Female
MH  - Fluorouracil/administration & dosage/analogs & derivatives
MH  - Humans
MH  - Kaplan-Meier Estimate
MH  - Male
MH  - Middle Aged
MH  - Mutation
MH  - Neoplasm Metastasis/drug therapy
MH  - Organoplatinum Compounds/administration & dosage
MH  - Oxaliplatin
MH  - Proto-Oncogene Proteins/genetics
MH  - Proto-Oncogene Proteins p21(ras)
MH  - Quality of Life
MH  - Treatment Failure
MH  - Vascular Endothelial Growth Factor A/*antagonists & inhibitors
MH  - ras Proteins/genetics
EDAT- 2009/02/07 09:00
MHDA- 2009/02/12 09:00
CRDT- 2009/02/07 09:00
PHST- 2009/02/07 09:00 [entrez]
PHST- 2009/02/07 09:00 [pubmed]
PHST- 2009/02/12 09:00 [medline]
AID - 360/6/563 [pii]
AID - 10.1056/NEJMoa0808268 [doi]
PST - ppublish
SO  - N Engl J Med. 2009 Feb 5;360(6):563-72. doi: 10.1056/NEJMoa0808268.